SUMMARY CORE A: ADMINISTRATIVE AND BIOSTATISTICS The Administrative Core (Core A) will provide clinical and scientific leadership, effective communication and fiscal and bio-statistical support to ensure the success of all Program Project activities. This proposal seeks to build upon our track record in genetically engineered T cell therapy by enhancing the chimeric antigen receptor T cell platform to specifically address systemic vulnerabilities that we have observed in our clinical trials to date. Our overarching hypothesis is that novel gene editing approaches can remove the remaining obstacles in the path of universally-available and universally-active CAR T cell therapy for hematologic malignancy. We have brought together a cadre of exceptional investigators who have collaborated and published together for many years. Each disease-focused project will be led by a recognized authority in the field. The three cores that support this proposal have been critical to the success of our clinical CAR T cell program to date and their expertise will underpin the success of this proposal. The centerpiece of each project is an innovative clinical trial that seeks to test our major hypotheses. We are leveraging the proven translational infrastructure, administrative staff and the centralized research organizations at the Center for Cellular Immunotherapies at the Perelman School of Medicine to achieve our objectives. Strong institutional commitment from the Abramson Cancer Center, Perelman School of Medicine and the University of Pennsylvania have facilitated our scientific and translational achievements. The essential services provided by Core A include: administrative support for all of the investigators in each project and core; fiscal management and oversight for all components of the Program Project; and organization and communication of all Program Project meetings and activities. The overall goal of this Core is effective and efficient leadership of the P01. The roles of the Director, Co-investigators and administrative staff are to facilitate communication and organizational structure while stimulating scientific and technological interactions. In order to achieve this goal, the Core has established four objectives: (1) To oversee the safety and monitoring activities for Penn and CHOP clinical sites; (2) To provide statistical support for clinical trials, projects and cores and implement plans to promote data sharing; (3) To coordinate the interactions among clinicians and scientists in projects and cores, internal and external advisory boards, and NCI personnel regarding effective implementation of proposed objective; (4) To provide budgetary services such as tracking expenses and providing investigator's monthly reports.